This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to establish the role of p53 protein in early kidney development, as aberrations during the early stages of development can lead to congenital defects. Recent studies show that loss of p53 in mice embryos causes kidney structure and growth abnormalities (kidney/ureter duplication, obstruction of ureter). Infants born with duplex kidneys may suffer from unilateral or bilateral vesicoureteral reflux, hydronephrosis, and cystic-dysplasia. A subset of p53-null/deficient mice exhibit profound defects in early renal development including duplex ureters/kidneys, hypoplasia and hydronephrosis. The etiology of these abnormalities is currently unknown. The objective of this proposal is to elucidate the role of p53 in early events of renal development with specific emphasis on UB outgrowth and patterning. The overall hypothesis is that p53 expression in the metanephric anlagen is required to restrict UB induction to one specific site along the nephric duct. In Specific Aim 1, the nephric cell lineage in which p53 expression is required to restrict UB induction to a specific site on the nephric duct will be determined by A) in situ hybridization, and B) Conditional deletion of the p53 ORF from either the UB or the MM using cre-lox transgenic mice. In Specific Aim 2, we propose to investigate the mechanisms by which p53 controls UB growth and branching. Identifying how p53 works in early kidney development will be an important step to formulating new therapies against congenital kidney diseases.